This application is in response to the RFA-AA-11-006 to provide support for the continuation of our consortium Integrative Neuroscience Initiative on Alcoholism: Stress, Anxiety and Excessive Drinking (a.k.a. INIAstress). Since its inception in 2002, INIAstress has had the primary goal of coordinating and facilitating translational, multidisciplinary and integrative research aimed at elucidating genetic and environmental influences on brain mechanisms that mediate excessive alcohol (ethanol) consumption, the response to stress, and the reciprocal relationship between excessive drinking, the physiological state of stress, and the subjective state of anxiety. Through this characterization we have helped to define factors that contribute to an individual's risk for the development of alcoholism, revealed underlying mechanisms and conditions that promote excessive and harmful drinking, and forged progress towards discovering novel, more effective, and tailored treatment strategies. In this renewal, we continue our cross-species approach and have further refined our INIAstress projects and cores to inform us about unique adaptations in brain circuitry following chronic intermittent ethanol exposure (ethanol-allostasis) that impact subsequent interaction of stress and ethanol to promote further excessive drinking. Collectively, these collaborative studies directly integrate behavioral, endocrine, neural and genetic data from animal models to humans within a scope of expertise and thematic inquiry that would not be possible using more traditional grant mechanisms (ROs or P50). PUBLIC HEALTH RELEVANCE: Stress and anxiety have long been implicated in the development of harmful drinking, its escalation to alcoholism and relapse to drinking following a period of abstinence. The INIAstress consortium uses a state-of-the-art translational approach (mice, monkeys and humans) to understand the complex interaction of stress and excessive drinking and identify novel, effective and tailored treatment strategies for alcoholism.